Protective effect of sauchinone by upregulating heme oxygenase-1 via the P38 MAPK and Nrf2/ARE pathways in HepG2 cells

Planta Med. 2010 Jan;76(1):41-7. doi: 10.1055/s-0029-1185906. Epub 2009 Jul 9.

Abstract

Sauchinone, a unique lignan isolated from the roots of Saururus chinensis (Lour.) Baill. (Saururaceae), is reported to exert potent hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. This study investigated the potency of sauchinone as a hepatic heme oxygenase (HO)-1 inducer and its protective effects in HepG2 cells. Treatment of the cells with sauchinone induced HO-1 expression and increased HO activity in a concentration- and time-dependent manner. This expression conferred cytoprotection against oxidative injury induced by T-butyl hydroperoxide. HO-1 expression by sauchinone also suppressed T-butyl hydroperoxide-induced reactive oxygen species generation in HepG2 cells. Moreover, sauchinone promoted the nuclear accumulation of the nuclear factor, E2-related factor 2 (Nrf2), and increased the promoter property of the antioxidant response element (ARE). Furthermore, treatment of the cells with a p38 MAPK inhibitor (SB203580) reduced sauchine-induced HO-1 expression and its protective effects. These results suggest that sauchinone increases the cellular resistance of HepG2 cells to T-butyl hydroperoxide-induced oxidative injury, presumably through the p38 MAPK pathway-Nrf2/ARE-dependent HO-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Benzopyrans / pharmacology*
  • Cell Nucleus
  • Dioxoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Heme Oxygenase-1 / metabolism*
  • Hep G2 Cells
  • Humans
  • Imidazoles / pharmacology
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology
  • Plant Roots
  • Protective Agents / pharmacology
  • Pyridines / pharmacology
  • Reactive Oxygen Species / metabolism
  • Response Elements / drug effects*
  • Saururaceae* / chemistry
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism*
  • tert-Butylhydroperoxide

Substances

  • Antioxidants
  • Benzopyrans
  • Dioxoles
  • Imidazoles
  • NF-E2-Related Factor 2
  • Plant Extracts
  • Protective Agents
  • Pyridines
  • Reactive Oxygen Species
  • sauchinone
  • tert-Butylhydroperoxide
  • Heme Oxygenase-1
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580